1. Field of This Invention
This invention relates to a process for the production of carnitine hydrochloride.
2. Prior Art
It is known to produce carnitine from acetoacetic ester. At the same time bromoacetoacetic ester is produced by bromation, the latter is converted by means of NaBH.sub.4 to .beta.-hydroxy-.gamma.bromobutyric acid ester. The latter is reacted with trimethylamine and the developing .gamma.-trimethylammonium-.beta.-hydroxybutyric acid ester bromide is saponified into carnitine hydrochloride [F. D'Alo and A. Masserini, Chemical Abstracts, Vol 60, 10777 g (1964)]. Because of the reduction with sodiumborohydride, this synthesis will probably remain limited for economic reasons merely to laboratory scale; moreover the yields are low.
It is known to use epichlorohydrin as a starting material. In such case, one proceeds in such a way that epichlorohydrin is first of all reacted with trimethylaminehydrochloride, the reaction product is converted with NaCN into the carnitine nitrile chloride and the latter is hydrolyzed to carnitine (see U.S. Pat. No. 3,135,788. In such process the products of all the intermediate steps are isolated. The yield amounts to about 74 percent.
The proposal has also been made to convert .gamma.-chloroacetoacetic acid anilide by reaction with trimethyl amine in an organic solvent, e.g., ethanol, into .gamma.-trimethyl ammonium acetoacetic acid anilide chloride, to hydrogenate the latter to .gamma.-trimethyl ammonium .beta.-hydroxy-butyric acid anilide chloride and then to convert the latter by means of aqueous hydrochloric acid into carnitine hydrochloride. A disadvantage of such a process lies in the fact that one must start out with .gamma.-chloroacetoacetic acid anilide, which must be produced in a preliminary step from .gamma.-chloroacetoacetic acid chloride. If in such a process one uses, instead of .gamma.-chloroacetoacetic acid anilide, .gamma.-chloroacetoacetic ester, then a mixture of various products develops, that is, mainly trimethylaminohydrochloride and succinylosuccinic acid ester.